This project, "Drug Treatment of Depressed Outpatients" is designed to ascertain, in a double-blind placebo-controlled study, whether plasma levels and/or saliva levels of imipramine, doxepin and/or their demethylated metabolites will be useful in determining appropriate dosages for patients 60 years of age and older. This will hopefully help the primary care physician as well as the psychiatrist to treat such patients with appropriate dosages of tricyclic antidepressants and minimal side effects. Two hundred patients above the age of 60 with a primary diagnosis of unipolar depression and without any significant medical problems will be admitted to the study over a four-year period. The biochemical parameters of depression and tricyclic antidepressants as well as plasma levels of the drugs and metabolites will be measured. The assessment battery will include psychiatric interview, a global assessment scale, several depression scales, and various measures of cognitive functioning. Progress will be monitored throughout the study.